Contraindications/Selected Warnings/Precautions

WARNING: SUICIDAL THOUGHTS AND BEHAVIORS

Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term studies. These studies did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in patients over age 24; there was a reduction in risk with antidepressant use in patients aged 65 and older.

In patients of all ages who are started on antidepressant therapy, monitor closely for worsening, and for emergence of suicidal thoughts and behaviors. Advise families and caregivers of the need for close observation and communication with the prescriber.

PRISTIQ is not approved for use in pediatric patients.

Contraindications

Hypersensitivity to desvenlafaxine succinate, venlafaxine hydrochloride, or any excipients in the PRISTIQ formulation. Angioedema has been reported in patients treated with PRISTIQ

Serotonin syndrome and MAOIs: Do not use MAOIs intended to treat psychiatric disorders with PRISTIQ or within 7 days of stopping treatment with PRISTIQ. Do not use PRISTIQ within 14 days of stopping an MAOI intended to treat psychiatric disorders. In addition, do not start PRISTIQ in a patient who is being treated with an MAOI such as linezolid or intravenous methylene blue

Selected Warnings and Precautions

Suicidal Thoughts and Behaviors in Children, Adolescents, and Young Adults: Monitor closely for worsening and for emergence of suicidal thoughts and behaviors

Serotonin Syndrome: Serotonin syndrome has been reported with SSRIs and SNRIs, including with PRISTIQ, both when taken alone, but especially when co-administered with other serotonergic agents (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John's Wort). If such symptoms occur, discontinue PRISTIQ and initiate supportive treatment. If concomitant use of PRISTIQ with other serotonergic drugs is clinically warranted, patients should be made aware of a potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases

Abnormal Bleeding: PRISTIQ may increase risk of bleeding events. Patients should be cautioned about risk of bleeding associated with concomitant use of PRISTIQ and NSAIDs, aspirin, or other drugs that affect coagulation

Angle Closure Glaucoma: The pupillary dilation that occurs following use of many antidepressant drugs including PRISTIQ may trigger an angle closure attack in a patient with anatomically narrow angles (Angle Closure Glaucoma) who does not have a patent iridectomy

Activation of Mania/Hypomania: Use cautiously in patients with Bipolar Disorder. Caution patients about risk of activation of mania/hypomania

Discontinuation symptoms were measured using the DESS checklist, a validated, clinician-rated instrument that includes 43 signs and symptoms associated with discontinuation or interruption of antidepressant treatment.2

In a pooled analysis of two 8-week studies:

During the first week after stopping PRISTIQ 50 mg, patients reported a mean score of 2.54 new or worsening symptoms vs 1.05 symptoms with placebo

The most common discontinuation symptoms experienced with PRISTIQ 50 mg were dizziness, nausea, diarrhea, and irritability.2

The Discontinuation-Emergent Signs and Symptoms (DESS) checklist is a validated, clinician-rated instrument that includes 43 items of signs and symptoms associated with discontinuation or interruption of antidepressant treatment. Patients are asked if they experienced a change in any of the symptoms on the list during the past 7 days. They are asked to characterize each symptom as new, old (but worse), old (but improved), or unchanged or not present. One point is scored for each new or worsened symptom, with a maximum score of 43.2

8-Week Studies
Pooled 50-mg data (n=317) vs placebo (n=636) from five double-blind, randomized, placebo-controlled, fixed-dose, 8-week studies of 50, 100, 200, and 400 mg qd of PRISTIQ in adults aged 18 or older with MDD (N=2001).5 The primary end point was the change in HAM-D17 total score vs placebo from baseline at week 8. Sexual function adverse reactions were recorded throughout the study for patients on placebo and PRISTIQ 50 mg.2,3,5

12-Week Study
Data from a double-blind, randomized, placebo-controlled, fixed-dose, 12-week study of PRISTIQ 50 mg qd (n=281) vs placebo (n=141) in adults aged 18 or older with MDD. The primary end point was the change in HAM-D17 total score vs placebo from baseline at week 12. The key secondary end point was SDS total score at week 12. Recording of sexual function was completed using the ASEX questionnaire at prespecified time points of baseline, 4, 8, and 12 weeks for patients on placebo and PRISTIQ 50 mg.2,6 Although the analysis was part of the a priori statistical plan, the study was not specifically powered to evaluate changes in sexual function. Intent-to-treat population shown.

8-Week Studies
Pooled 50-mg data (n=308) vs placebo (n=623) from five double-blind, randomized, placebo-controlled, fixed-dose, 8-week studies of 50 mg, 100 mg, 200 mg, and 400 mg qd of PRISTIQ in adults aged 18 or older with MDD (N=2001). The primary end point was the change in HAM-D17 total score vs placebo from baseline at week 8. Weight gain was measured at prespecified time points during the course of these studies. Statistical significance was calculated vs placebo (P<0.05) based on change from baseline to end point; observed cases. Clinically significant weight change reflects analysis from five pooled studies of PRISTIQ 50 mg (n=309) vs placebo (n=623).2,5,12

12-Week Study
Data from a double-blind, randomized, placebo-controlled, fixed-dose, 12-week study of PRISTIQ 50 mg qd (n=282) vs placebo (n=141) in adults aged 18 or older with MDD. The primary end point was the change in HAM-D17 total score vs placebo from baseline at week 12. Weight gain was measured at prespecified time points during the course of these studies. Statistical significance was calculated vs placebo (P>0.05) based on change from baseline to end point; observed cases.2

**Weight gain was measured at prespecified time points during the course of these studies; observed cases analysis.2 Statistical significance was calculated vs placebo based on change from baseline to end point; observed cases.2,7

††Pooled analysis of five 8-week studies. Of the five studies, two examined 50 mg and 100 mg; one examined 100 mg, 200 mg, and 400 mg; and two examined 200 mg and 400 mg5

‡‡Clinically significant weight change was defined as an increase or decrease of ≥7% from baseline. Weight change was measured at prespecified time points during the course of these studies.2

Patients receiving PRISTIQ should have regular monitoring of blood pressure, since increases in blood pressure were observed in clinical studies

Pre-existing hypertension should be controlled before initiating treatment with PRISTIQ. Caution should be exercised in treating patients with pre-existing hypertension, cardiovascular, or cerebrovascular conditions that might be compromised by increases in blood pressure

Cases of elevated blood pressure requiring immediate treatment have been reported with PRISTIQ. For patients who experience a sustained increase in blood pressure while taking PRISTIQ, either dose reduction or discontinuation should be considered

The table shows the percentage of patients who exceeded a predetermined threshold value during placebo-controlled, short-term studies in MDD. N values represent range of patients for whom variables were evaluated

Elevations in fasting serum total cholesterol, LDL (low-density lipoprotein) cholesterol, and triglycerides occurred in the controlled studies. Some of these abnormalities were considered potentially clinically significant

Indication

PRISTIQ Extended-Release Tablets are indicated for the treatment of major depressive disorder in adults.

Important Safety Information for PRISTIQ

WARNING: SUICIDAL THOUGHTS AND BEHAVIORS

Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term studies. These studies did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in patients over age 24; there was a reduction in risk with antidepressant use in patients aged 65 and older.

In patients of all ages who are started on antidepressant therapy, monitor closely for worsening, and for emergence of suicidal thoughts and behaviors. Advise families and caregivers of the need for close observation and communication with the prescriber.

PRISTIQ is not approved for use in pediatric patients.

Contraindications

PRISTIQ is contraindicated in patients with a known hypersensitivity to PRISTIQ or venlafaxine. Angioedema has been reported in patients treated with PRISTIQ.

Serotonin syndrome and MAOIs: Do not use MAOIs intended to treat psychiatric disorders with PRISTIQ or within 7 days of stopping treatment with PRISTIQ. Do not use PRISTIQ within 14 days of stopping an MAOI intended to treat psychiatric disorders. In addition, do not start PRISTIQ in a patient who is being treated with an MAOI such as linezolid or intravenous methylene blue.

Selected Warnings and Precautions

All patients treated with antidepressants should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the first few months of treatment and when changing the dose. Consider changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse or includes symptoms of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, mania, or suicidality that are severe, abrupt in onset, or were not part of the patient's presenting symptoms. Families and caregivers of patients being treated with antidepressants should be alerted about the need to monitor patients.

The development of a potentially life-threatening serotonin syndrome has been reported with SSRIs and SNRIs, including with PRISTIQ, both when taken alone, but especially when co-administered with other serotonergic agents (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John's Wort) and with drugs that impair metabolism of serotonin (in particular, MAOIs, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue). If such events occur, immediately discontinue PRISTIQ and any concomitant serotonergic agents, and initiate supportive treatment. If concomitant use of PRISTIQ with other serotonergic drugs is clinically warranted, patients should be made aware of a potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increase.

Patients receiving PRISTIQ should have regular monitoring of blood pressure, since increases in blood pressure were observed in clinical studies. Pre-existing hypertension should be controlled before starting PRISTIQ. Caution should be exercised in treating patients with pre-existing hypertension, cardiovascular or cerebrovascular conditions that might be compromised by increases in blood pressure. Cases of elevated blood pressure requiring immediate treatment have been reported. For patients who experience a sustained increase in blood pressure, either dose reduction or discontinuation should be considered.

SSRIs and SNRIs, including PRISTIQ, may increase the risk of bleeding events. Concomitant use of aspirin, NSAIDs, warfarin, and other anticoagulants may add to this risk.

The pupillary dilation that occurs following use of many antidepressant drugs including PRISTIQ may trigger an angle closure attack in a patient with anatomically narrow angles (Angle Closure Glaucoma) who does not have a patent iridectomy.

PRISTIQ is not approved for use in bipolar depression. Prior to initiating treatment with an antidepressant, patients should be adequately screened to determine the risk of bipolar disorder.

PRISTIQ should be used cautiously in patients with a history or family history of mania or hypomania or with a history of seizure disorder.

On discontinuation, adverse events, some of which may be serious, have been reported with PRISTIQ and other SSRIs and SNRIs. Abrupt discontinuation of PRISTIQ has been associated with the appearance of new symptoms. Patients should be monitored for symptoms when discontinuing treatment. A gradual reduction in dose rather than abrupt cessation is recommended whenever possible.

Hyponatremia may occur as a result of treatment with SSRIs and SNRIs, including PRISTIQ. Discontinuation of PRISTIQ should be considered in patients with symptomatic hyponatremia.

Interstitial lung disease and eosinophilic pneumonia associated with venlafaxine (the parent drug of PRISTIQ) therapy have been rarely reported.

Important Safety Information for PRISTIQ (desvenlafaxine)

WARNING: SUICIDAL THOUGHTS AND BEHAVIORS

Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term studies. These studies did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in patients over age 24; there was a reduction in risk with antidepressant use in patients aged 65 and older.

In patients of all ages who are started on antidepressant therapy, monitor closely for worsening, and for emergence of suicidal thoughts and behaviors. Advise families and caregivers of the need for close observation and communication with the prescriber.

PRISTIQ is not approved for use in pediatric patients.

Contraindications

PRISTIQ is contraindicated in patients with a known hypersensitivity to PRISTIQ or venlafaxine. Angioedema has been reported in patients treated with PRISTIQ.

Serotonin syndrome and MAOIs: Do not use MAOIs intended to treat psychiatric disorders with PRISTIQ or within 7 days of stopping treatment with PRISTIQ. Do not use PRISTIQ within 14 days of stopping an MAOI intended to treat psychiatric disorders. In addition, do not start PRISTIQ in a patient who is being treated with an MAOI such as linezolid or intravenous methylene blue.

Selected Warnings and Precautions

All patients treated with antidepressants should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the first few months of treatment and when changing the dose. Consider changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse or includes symptoms of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, mania, or suicidality that are severe, abrupt in onset, or were not part of the patient's presenting symptoms. Families and caregivers of patients being treated with antidepressants should be alerted about the need to monitor patients.

The development of a potentially life-threatening serotonin syndrome has been reported with SSRIs and SNRIs, including with PRISTIQ, both when taken alone, but especially when co-administered with other serotonergic agents (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John's Wort) and with drugs that impair metabolism of serotonin (in particular, MAOIs, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue). If such events occur, immediately discontinue PRISTIQ and any concomitant serotonergic agents, and initiate supportive treatment. If concomitant use of PRISTIQ with other serotonergic drugs is clinically warranted, patients should be made aware of a potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increase.

Patients receiving PRISTIQ should have regular monitoring of blood pressure, since increases in blood pressure were observed in clinical studies. Pre-existing hypertension should be controlled before starting PRISTIQ. Caution should be exercised in treating patients with pre-existing hypertension, cardiovascular or cerebrovascular conditions that might be compromised by increases in blood pressure. Cases of elevated blood pressure requiring immediate treatment have been reported. For patients who experience a sustained increase in blood pressure, either dose reduction or discontinuation should be considered.

SSRIs and SNRIs, including PRISTIQ, may increase the risk of bleeding events. Concomitant use of aspirin, NSAIDs, warfarin, and other anticoagulants may add to this risk.

The pupillary dilation that occurs following use of many antidepressant drugs including PRISTIQ may trigger an angle closure attack in a patient with anatomically narrow angles (Angle Closure Glaucoma) who does not have a patent iridectomy.

PRISTIQ is not approved for use in bipolar depression. Prior to initiating treatment with an antidepressant, patients should be adequately screened to determine the risk of bipolar disorder.

PRISTIQ should be used cautiously in patients with a history or family history of mania or hypomania or with a history of seizure disorder.

On discontinuation, adverse events, some of which may be serious, have been reported with PRISTIQ and other SSRIs and SNRIs. Abrupt discontinuation of PRISTIQ has been associated with the appearance of new symptoms. Patients should be monitored for symptoms when discontinuing treatment. A gradual reduction in dose rather than abrupt cessation is recommended whenever possible.

Hyponatremia may occur as a result of treatment with SSRIs and SNRIs, including PRISTIQ. Discontinuation of PRISTIQ should be considered in patients with symptomatic hyponatremia.

Interstitial lung disease and eosinophilic pneumonia associated with venlafaxine (the parent drug of PRISTIQ) therapy have been rarely reported.